PMID- 11356643 OWN - NLM STAT- MEDLINE DCOM- 20010614 LR - 20200930 IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 280 IP - 6 DP - 2001 Jun TI - Homocysteine induces monocyte chemoattractant protein-1 expression by activating NF-kappaB in THP-1 macrophages. PG - H2840-7 AB - Homocysteinemia is an independent risk factor for cardiovascular disorders. The recruitment of monocytes is an important event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates monocyte migration into the intima of arterial walls. The objective of the present study was to investigate the effect of homocysteine on MCP-1 expression in macrophages and the underlying mechanism of such effect. Human monocytic cell (THP-1)-derived macrophages were incubated with homocysteine. By nuclease protection assay and ELISA, homocysteine (0.05-0.2 mM) was shown to significantly enhance the expression of MCP-1 mRNA (up to 2.6-fold) and protein (up to 4.8-fold) in these cells. Homocysteine-induced MCP-1 expression resulted in increased monocyte chemotaxis. The increase in MCP-1 expression was associated with activation of nuclear factor (NF)-kappaB due to increased phosphorylation of the inhibitory protein (IkappaB-alpha) as well as reduced expression of IkappaB-alpha mRNA in homocysteine-treated cells. In conclusion, our results demonstrate that homocysteine, at pathological concentration, stimulates MCP-1 expression in THP-1 macrophages via NF-kappaB activation. FAU - Wang, G AU - Wang G AD - Department of Pharmacology and Institute of Cardiovascular Science and Medicine, Faculty of Medicine, University of Hong Kong, Hong Kong, China. FAU - Siow, Y L AU - Siow YL FAU - O, K AU - O K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (Antibodies) RN - 0 (Chemokine CCL2) RN - 0 (DNA-Binding Proteins) RN - 0 (I-kappa B Proteins) RN - 0 (NF-kappa B) RN - 0 (NFKBIA protein, human) RN - 0 (RNA, Messenger) RN - 0 (RNA, Ribosomal, 28S) RN - 0LVT1QZ0BA (Homocysteine) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - 2104-86-1 (Tosyllysine Chloromethyl Ketone) RN - 9007-49-2 (DNA) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Antibodies/pharmacology MH - Binding, Competitive/drug effects MH - Cell Line MH - Chemokine CCL2/antagonists & inhibitors/*biosynthesis/genetics MH - Chemotaxis/drug effects MH - DNA/metabolism MH - DNA-Binding Proteins/biosynthesis/genetics MH - Dose-Response Relationship, Drug MH - Enzyme-Linked Immunosorbent Assay MH - Gene Expression/drug effects MH - Homocysteine/*pharmacology MH - Humans MH - *I-kappa B Proteins MH - Macrophages/cytology/*drug effects/*metabolism MH - NF-KappaB Inhibitor alpha MH - NF-kappa B/antagonists & inhibitors/*metabolism MH - RNA, Messenger/metabolism MH - RNA, Ribosomal, 28S/metabolism MH - Tosyllysine Chloromethyl Ketone/pharmacology EDAT- 2001/05/18 10:00 MHDA- 2001/06/23 10:01 CRDT- 2001/05/18 10:00 PHST- 2001/05/18 10:00 [pubmed] PHST- 2001/06/23 10:01 [medline] PHST- 2001/05/18 10:00 [entrez] AID - 10.1152/ajpheart.2001.280.6.H2840 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2001 Jun;280(6):H2840-7. doi: 10.1152/ajpheart.2001.280.6.H2840.